Note: Descriptions are shown in the official language in which they were submitted.
2~1122~
BIOLOGICALLY ~CTIVE ~TERIAL, ~I~THOD FOR ~RE;PARI~G
SAME, AND DRESSING M~ANS
The present invention relates to the art of medicine and,
more specifically, to a biologically active material, to a methc
, `
`~ for preparing said material, and to a dressing means based on
said material.
i The present biologically active material may be widely used
for treating traumata, frostbites, trophic ulcers, pyo-necrotic
wounds,and diseases which are accompanied by the formation of
necrotic sections and by accumulation of thiek, viscous exudate,
and it may be applied in surgery, dentistry, urology, proctolog~
. ~astroenterology. Furthermore, the present biolo~ically active
material is applicable in veterinary, biotechnology, for instan-
; ce, as a sorbent for recovering trypsin~ antitrypsin inhibitc
;, State of the Art
It. i8 known in medical practice to use native proteolytic
en7.yme preparations for treating pyo-inflammatory diseases.
However, æuc.h enzymes are expen~ive and in short supply. Regard-
less of their certain effectiveness, such enzymes are not
. . .
resi~tant against inhibitors which are rontained in wound di~-
charge, nor are they resistant against pH and temperature varia-
tions. Moreover, said enzyme~ posses~ antigenic (aller~ic)
and pyrogenic properties.
~ There is known in the prior art a film material (Cf. SU
Inventor's Certificate No. 700,138, issued on November 30, 1979
having biological activity and containing a carrier, such as
-.,~' ' '
':
-2- 201~22~
cellulose triacetate or secondary acetate, and a proteolytic
enzyme, such as, for instance, tryp~in, ~ -chymotrypsin, said
components being taken in the following ratio:
cellulose triacetate (secondary acetate) - 80 - 99a/1 by weig~
enzyme - balanc-s.
The above-cited film material is prepared by emulsifying ~-
an aqueous solution of a proteolytic enzyme in a cellulose
ester solution in a water-immiscible organic solvent, followed
by forming a film. In the film material thu~-prepared, the
proteolytic enzyme occurs in the form of finest inclusions.
The above-described material is capable of producing a long- -
sustained necrolitic e~.fect due to gradually releasing small
doses of the enzyme from the film surface. '~'7''_'._..
However, once the enzyme has been releas~d from the materia]
the ehzyme exhibits all the properties of a native material,
including all of it~ disadvantages, namely, non-stability
against inhibitors, against pH and temperature variations,
antigenecity and pyrogenecity. And finally, it is necessary
to note that the enzyme consumption rate is high - up to 20
by weight.
Application of this material is sestricted by the high pro-
bability rate for enzyme inactivation in organic solvents
which are used for forming films or monofilaments. The mate-
rial itself can be used only as a draining material~ and it
cannot be used as a dressing material.
Also known in the art ~s a granular material (Cf., e.g.
laid-open French Patent No. 2,556,222; issued on June 14,1986)
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~3~ 201~22~
possessing a biolo~ical activity and containing a carrier, such
as dextran, chitin, chitosan, and, immobilized thereon9 an
en7.yme, such as chymotrypsin, trypsin, said components being
present in the following weight ratios: carrier - 80.0~ 80.5
weight, enzyme - balance. The abo~e-cited material exhibits
a prolonged action, and the enzyme contained in it has no possi
bility to penetrate into a blood channel and manifest antige-
necity.
The cited material is also disadvantageous in that it has
an elevat~ed enzyme content, namely, up to 20~ by weight, and
i9 expensive. Apart from it, this material calls for the use
of special installations and apparatuses for its storing in
specially prepared buffer solutions at lower temperatures
(at 2C)
-Equally known in the art is a method for preparing a biologi
cally active material (Cf. SU Inventor~ Certificate-No. 700,_
;~ 138; issued on November 30, 1979), which comprises the follow-
ing steps of:
- preparing an aqueous solution of a proteolyti~ enzyme,
preferably, trypsin;
- preparing a solution of cellulose ether~ in the present
; case, cellulose triacetate, in a water-immiscible organic
solvent;
- emul~ifying the former solution in the latter one;
:::, - :.
i - shaping the material into medicinal forms, such as plates,
J
films, etc., using a dry-forming method;
- holding the medicinal forms thus-obtained for 1 hour in a
.
. :
2011~2~
; vacuum drier at a temperature of 25 C.
The materials prepared ~y the above-cited method possess a
1~iological activity and contain components in the ~ol]owing
weight ratio~, in per cent by weight:
- cellulose triacetate or ~econdary acetate - 80 to 99
- trypsin - balance (1 to 20).
The latter method suffers from a number of serious disadvan-
tages:
- a considerable enzyme consumption rate (up to 20%3;
- a partial loss of the enzymatic activity during emulsifi-
cation in an organic solvent;
- absence of a chemicaI bond between an enzyme and a carrier
owing to the fact that the enzyme is physically incorporated
into the structure of the material;
- release of the enzyme into wound discharge in the form
of a native preparation, which may result in a negative side
effect, such as, for instance, allergic reactions; and
- need for the use of specially designed equipment, such as
a vacuum drier.
The material prepared by the~ above-cited method in the form
of plates cannot be used as a dressing material, since it does
not possess the requisite sanitary and hygienic properties,
such as hygroscopicity, air permeability, elasticity, etc.,
and it can be used only as a draining material. -
Also known in the prior art is a method for preparing a
- biologically actiYe material (Cf. laid-open French Patent ~o.
2,550,222, issued on June 14, 1985; laid-open F.R.G. Patent
, . . .
.. :
,. ~.
201~22~
No. 3,444,746, issued on June 20, 1935; and Czechoslovakian
Inventorfs Certificate No. 249,311, issued in 1988), which com-
prises the following steps of:
- preparin~ particulate material (carrier), such as cross-
linked dextran, chitin, chitosan, by causin~ them to swell
in water;
- preparing.an ac.tivating solution of 2-amino-4,6-dichloro-
-s-triazine in acetone, followed by dilution with water at 50 C
- activating the material with an activating solution at
50 C under stirring conditions;
~` - adding to the activating solution containing said material
. an aqueous solution of sodium carbonate and hydrochloric acid
and stirring at 50 C;
- filtering the resmlting mixture;
- washing the remaining material with an aqueous solution
of acetone and water to obtain an ac.tivated material which
can be stored in a phosphate buffer at 2 C;
., ~. .
- preparing an enzyme solution, such as, for instance, a
' chymotrypsin solution~ in a bu~fer; ~
.~ - immobilizing the enzyme on the activated material~ such ~
cross-linked dextran, chitin,.chitosan; ~.
:::
- washing the material containing, immobilized thereon, ~:
chymotrypsin. in turn, with borate and acetate buffer solutionc
containing sodium chloride at different concentrations; ~ .
- washing the material with a borate.buffer solution without .
sodium.chloride; and
-lyophilizing the material with the enzyme immobilized there~
~, :
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-6- 201i22~
The above-cited methods made it pos3iblc to produce biologi-
cally acti~e materials~ their components being taken in the
following weight ratios~ per cent by weight:
. - enzyme - 19.5 t.o 20
- carrier - balance.
The above method suf~ers from the following essential limi-
tations:
- a considerable enzyme consumption rate (up to 20%);
- a multi-step production technology and, as a result, poor
efficiency and high cost;
. - need for the use o~ short-supply and e~otic raw materials,
.. . ,.~ -~
. such as, for instance, chitin obtainable from crab shells or
....
. from myce~lium of Penicillium chrvsogenu~ fungus; and
~.i
~; - need. for the use of specially designed equipment for
': ~toring the acti~ated material and for carrying out the. lyophi- .
.:~ lization step.
" The biologically active material prepared by the above-cited
~ method.cannot be used as a dressing one, and i.t is usable
:~ for~ of a
~I only in th~ powder or a suspension,. since in its finiished form
.. ~ the cited material represents a powder containing an immobilize .~:
, I -
enzyme having a particle size.o~ from 0.01 to 0.5 mm. .
There is known in the prior art a biologically active dress~
: ing means (C~. British Patent No. 2,092,006, ~sssed on Februar~
.`1 11, 1986~, comprising, arranged in succession therein, a pro-
. . - . .
tective layer, an absorbing layer, and a wound-adJoining layer.
-, This dressing means comprise~ a thin layer of the enzyme
applied to the internal side o~ the wound-adjoining layer. The
,,~
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~7~ 201~22~3
protective layer can be made in the form of a woven or non-~over
material.
The absorbing layer can be made from cotton, or viscose (cot-
ton wool)~ or rayon.
The wound-adjoining layer i.s made in the form of woven or
non-woven textile materials~ or perforated polyester, polyamide,
polyurethane, polyethylene, polypropylene and cellulose triace-
tate film, and it contains metallic copper or copper compounds.
~' As the wound discharge comes to contact with the above-
cited dressing means~ all of the negative properties of the
I enzyme become manifest as those of a native enzyme, in particu-
lar, :~t~s~ instability against inhibitors which are contained
in the wound discharge, against pH and temperature variations~
' antigenecity aIld pyrogenecity, high cost owing to a high enzyme
3i, consumption rate.
Brief Desciption of the.Essence of the Invention
.; It is the object of the present i~lvention to develop smch a :
biologically ac.tive material as would ensure the prolonged
J
- action of the medicinal substances contained therein, be amenabl
~, to storing for a long time in packages in air-dry state under
normal condition~, while retaining all the sanitary and hygienic
propertie~ characteristic of a dressing material, would secure
a medical effect within a shorter period of treatment at a
~ lower content of a biologi¢ally active principle, and would be
` capable of being effectively used as a dressing means.
Another object of the present invention is to develop such : ~
a method for preparing a biologically active material as would .
., :
. ' ' ~
~ -8- 201122~
enable the production of a l~laterial ~or use as a dreissing means
: wo~lld be technologically simple, would not be expensive and
would not call for high material ~xpenses due to use of readily
available materials, and could be easily adaptable under commer
cial-scale production conditions.
A further object of the inventio.n is to provide a dressing
. mean ~ hich would ensure a high medical effect at a considerably
i smaller enzyme consumption rate, would be resistant to inhibi-
tors which are contained in the wound discharge~ to pH and
temperature variations, and would be free from antigenic and
pyro~enic properties.
~ The abo~e-formulated objects ha~e.been achieved by providing
-.~ a biologically active material compristng a carrier and, immo-
`I bilized thereon, an enzyme., which material, in accordance with ~-
.~ ,
, the invention,. comprises, as said carrier, a textile material, .~:
., :
while said enzyme is: bound to said carrier by a co~alent bond~
.: the componentsi of the material being present in the following
~ weight ratios, per cent by weight~
.
.~ - enzyme - 0.02 to 0.50 :::
i~ ,: ::
q - carrier - gg.98 to 99.50
.~ The textile material is used fo~ the reason that it has a ~
~- weakly pronounced: medical effeet, since it ïs capable of drain- -
. ing the wound~ of adsorbing microbes and:toxins~ of prote¢ting
the wound surface from contamination, and of preventing from ~ ~
.:i exce3sive loss of moisture. ~ ~.
The above-specified weight ratios are determined by the
fact that the use of a biologicQlly active material containing :~
, I
.. ~
: j . .......... - -
~,. : :. . ~ : ~ , -: :: .
9- 20~122~
an enzyme in an amount of below 0. 02~o by weight ~harply reduces
the medical effect (by more than a factor of 1.5), whereas
the use of a material containing more than 0.50$ by weight of
an enzyme does not considerably shorten the duration of treat-
ment (an average treatment period lasting 14 + 2 days), but,
instead, sharply augments the cout of the material and
treatment.
In medical practice, it is advisable that the period of a
single application of the claimed material to the wound be from
., .
48 to 96 hours. - -
The medical efficacy of the present material, if it is store
in packaged state under normal conditions (i.e. at room tempera
ture of about 20 C), is retained for a period of not less
than 5 years.
The use of the material in accordance with the~present -
invention makes it possible to shorten the period of healing
wounds by an average factor of 1.5 at doses which are 10 to
30 times smaller-than those~ normally u~ed for healing wounds
by means of the conventional biologically active materials
or native enzymes. The claimed material is not toxic, nor does
it cause any allergic reactions.
It- is ad~isable that the textile material would represent
a woven, or non-woven, or knitted fabric.
It is possible that the textile material be made of natural
.:... . . .
fibres-, which provides for better conditions for application
, of the present material onto the wound surface, close to com-
.' :
~ fortable conditions.
.
: :
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_ 1 ir)_
201122~
In order to e~pand the range of raw materials potentially
amenable for the use by the present inveintion, it is adivsable
' that the textile carrier be made of ~ynthetic or man-made ~i~re
i It is also advisa~le that the material in accordance with
the present invention would contain, as an enzyme, proteolytic,
or c.ollagenolytic~ or bacteriolytic en~ymes, since these enzyme
make it possible to split denaturated proteins having various
, structures.
l~ It is also advisable that the present biologically active ~.
material be turned out in the form: o.f lint: having fibres 1.0
~l~ to 15 mm long~ whereby it becomes possible to use the material .
; in stomatology and for treating deep wounds, including puncturec :~
i purulent wounds o~ Gomplicated configurations.
' It is also possible that the p~esent material be turned ::
out in the form of a powder ha~ing a particle size of from
0.001 to 1.00 mm, whereby it becomes possible to use it for
.i treating extensive wound sur~aces of complicated configurations
~'i The present material is suitable. for treatment of pyo-ne~ro~
`~ tic wounds, acute and chronic forns of periodontitis, wounds
having complicated configurations and cavities, hollow organs
~ of a live organism having narrow excretory channels, for
~: instanc.e, for treating inf?ammatory processes in the urinary
bladder cavity.
The approbation of the.present ~aterial under the conditions
of tests and clinical observations ha~ demonstrated its high
biological and therapeutic activityl Special studies have shown
.
, that the present material shows a peak of its therapeutic
.. , :
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~ - 20~22~
.~
activity, when applied onto the wound surface, for 4 days from
the moment of application.
The test animals have shown no signs of allergic reactions
after the application o~ the biologically active l~-aterial
: . :
prepared in accordance with the present invention. Nor have
been observed such changes in the hemostasis functions as the
level o~ fibrinogen degradation products~ fibrino~en content,
aad fibrinolytic activity.
The above-described biologically active material is prepared
by a method comprising the steps of activating a carrier, immo-
bilizing thereon an enzyme using a buffer solution, followed
by washing, drying and shaping the material thus-prepared into
medicinal forms. In accordance with the present invention~
the step of activating a carrier, namely, a textile material,
is carried out by forming therein reactive (reaction-capable)
functional groups until the~amount of such groups reache~
0.0625 to 3.125 mg-equiv. per gram of the carrier. The immobi-
lization treatment of the enzyme is carried out from a buffer
solution having a-pH of from 6.g to 7.5 at room temperature
for 8 to 16 hours to form a ~ovalent chemical bond between
the textile material and enzyme, whereupon the material thus-
prepared is squeezed out, washed until no enzyme traces are
detected in the washings, dried at room temperature (at about
20 C), placed into a container, and sterilized.
The present method is distinguishable over the prior-art
ones in that it is simple and cheap in its realization in term
of its engineering aspect and the equipment required for its
implementation.
,', ` : ~
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201~ 22~
.
~ The claimed method ~lakes it possible to prepare a material
which conllines the properties of a rnedicinal pr0paration with
those of a dressillg means, and which retains all the sanitary-
-and-hygienic and physico-chemical properties of the starting
dressing ;naterial. :~
~ The biologically acti~e material thus-prepared retains its ~ ~
.~ hi~h therapeutic efficacy while being stored under normal ~ p
conditions in packaged state for a period of at least 5 ye 9,
It is advisable that acti~ation of a c.ellulose-containing : :
.
~ ,
~' textile carrier be carried out by subjecting it to oxidation :~
. ~
` with an alkali metal periodate to ~orm cellulose dialdehyde
containing reactive functional aldehyde groups in an amount .
of from o.o6z5 to. 3.125 mg-equiv. per gram of a carrier,
~ It is preferable that activation of a textile carrier made
`' of synthetic fibres be conducted by subjecting the carrier
to hydrolysis with acid, followed by washing the carrier thus-
~ hydrolyzed and by reacting it with.a solution containing reacti~
`'! funct.ional groups until the amount of the latter in the carrier
~ reacles from o,o625 t.o 0,.3125 mg-equiv. per gram of the carrier
:l It is advisable that the treatment of the hydrolyzed carrier
made of synthetic. fibres be carried out either with.a glutaric
.~ aldehyde ~olution, followed by washing with water, or with a :;~
dimethyl sulphate solution, followed by washing the carrier :~
.~ in ethanol and in a phosphate buffer solution. ~. -
. .,
The above-formulated objects are accomplislled owing to ~he
fact that in a dressing means in the form of a bandage compris-
ing, arranged in succession therein, a protecti~e layer, an ~-
~' `, r
_13_
20~122~
absorbit~g layer, and a ~ound-acljoining layer, in accordance
with the invention, at least one l~yer is made from the above-
, described biolo~ically active material.
! It i9 advisable that in said dressing means the wound-adjoin-
A . ,
ing layer be formed from the above-described biologically
active material, while said absorbing layer be formed from a
textile material.
It is preferable that in the dressing means the wound-adjoin-
ing layer be formed from said biologically active material, ~-
in which proteolytiOE, or collagenolytic~ or bacteriolytic
enzymes are used, while the absorbing layer be also formed
from said material, in which collagenolytic or bacteriolytic
enzymes are used, the enzymes used in both of said layers being
different from each other.
Application of the above-described dressing means during
the period of a few hours after a trauma (an injury~ makes it
possible to prevent it from infecting and to shorten the
period of subsequent treatment by 2 to 4 days.
Detailed Description of the Invention
, The biologically actiYe material comprises, as a carrier,
a textile material and an immobilized enzyme which is bound to
this textile material by a covalent bond, the enzyme and textil~
material being present in the following weight ratios, per cent
j by weight:
- enzyme - 0.02 to 0.50
- textile material - 99.98 to g9.50.
The textile material may be made from natural fibres, such a
-14-
2~22~
for instance, cotton, linen, silk, wool fihres, or from synthe-
tic fibreg, such as, for instance, polyacrylonitrile, polycapro : ~:
amide, polyurethane fibres, or from man-~ade fibres, such as, ~:
for instance~ triacetate, celllllose secondary acetate, viscose
~ fibres.
The textile material may be in the form of, for instance,
:. woven, or non-woven, or knitted fabric.
As said enzymes~ the present material may make use~ of proteo~-
. lytic enzymes, such as, for instance, hygrolytin, protosubtilin
terrilytin, trypsin, or collagenolytic enzymes~, such as, for
~; instance, c.ollagenase, or bacteriolytic enzymes, such as, for
instance, lysozyme.
The specific choice for practical application of the abo~e-
mentioned groups of immobilized enzymes is conditioned by
their therapeutic properties.
It. is advisable that the proteolytic enzymes, such as, for
instance, trypsin, be applied at the hydration stage of treat-
ment of pyo-necrotic woundY, that is, when it. is necessary to.
, split (cleav~) necrotic masse~ to liquefy viscous dense exu-
;i date, etc.
~ The bacteriolytic enzymes, such as, for instance, lysozyme~
.. are recommended; for suppression of microbial growth in the woun
The collagenolytic enzymes, suc.h as, for instance, col].agena
se, exhibit both proteolytic and collagenolytic activity and~
as such~ they are particularly effective in treatment of burn-
~1 induced diseases.
In the light of the foregoing, it will be understood that
:~
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~ -15-
20~22~
in view of the extrei11e variety of various pyo-necrotic and
inflammatory processes, there i9 a need for biolozically active
materials containing immobilized enzymes having different natur
and therapeutic properties.
Dependin~ on the con~iguration of a wound or a channel
through which the biologically active material i3 supplied to
the wound surface~ said material may assume various ~edicinal
forms, namely, cloth, banda~es, napkins, lint having fibres
1.0 to 15 mm long, and powder having particles with sizes rang-
ing from 0.001 to 1.0 mm,
The study Q~ bacterial inoculations from wounds prior to
and after the use of the present material made it possible
to arrive at well substantiated conclusions, to-wit: the range
of inoculated microorganisms bec~me narrower, the virulence
of the sown microorganisms weakened due to their substitution
by a less pathogenic flora, their resistance to antibiotics
weakened. Application of the present material lowers the level
..
of bacterial dissemination of wound surfaces, the period of
preparing patients for plastic operations and the period of
staying of patients at stationary hospitals become shorter by
10 days on the average.
During the entire period of treatment, patients~' urine and
blood were analyzed, their temperature was taken. None of the
cases showed any sign~ of general or local complications which
would be caused by the application of the present material.
The present material underwent testing under clinical condi-
tions for treating 3200 patients affected with pyo-necrotic
.:
~ -16-
~ 20~ 122~
diseases, frostbites, trophic ulcers, etc.
The present material was ap~plied locally following the pro-
cedure as described below: after a preliminary surgical treat-
ment, such as dissection of the pyo-necrotic area, opening of .
pockets, dissection of intersections and for~ation of a single
cavity, the proposed biologically active .naterial, for instance,
. in the form.of napkins, cotton wool (lint) impregnated.with a
physiologic salt solution, was incorporated into the wound.
It has been established that, when the present material was
~. applied, the period of healing the wounds was reduced to 15 + 2.
days, whereas during treatment by a eonventional method using
a hypertonic salt solution c.ontaining antiseptics of a control ~:
batch of patients (3110 patients~, this period was 26 + 2.2
days~ that is, application of the present material makes it
possible t:o accelerate the c.ourse of treatment by an average
.,
~j factor of 1.5.
.~ None of the cases of clinical application of the present
j",~l .
j material showed. any toxic: or allergic reactions.
The present material i9 highly atraumati.c due to the~presenc(
on its surface of a co~alently bound enzyme. The effort require
: 'l
:~f for breaking off the present material fro~l the wound surface
~.~ is on the average half as that of the non-modified commonly
:. applied dressing material.
j The results of the clinical application of the claimed mate-
"3 rial have shown the following:
, .
- its high effectiveness for treatillg pyo-necrotic processes
' the curing period became 1.3-1,8 times shorter;
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20~22~
; - it~s high atraulnaticity: the f`orce of breaking the material
off the wound surface is half as much;
; - a lower enzyme consumption rate: 10 to 30 times less as
compared to that of native enzymeq used for treating the same
:. ~
diseases; not less than 25 times as compared to the art-known
analogues (in the analogues the enzyme content is 0.5 to 20~o~
whereas in the present therapeutic Inaterial the enzyme content
is 0.02 to 0.5$3.
The stability tests of the present material a~ter its steri-
~, lization ha~e shown that the present material preserves its
curative effect after having been stored in packaged state
, under normal conditions (i.e. at 20 C) for a period of at
least 5 years, all of its physico-mechanical and sanitary-and-
~' -hygien~c pr~perties being retained.
The present material has no side effects and contraindica-
tions for its application.
~! The clini~al effectiveness of application of the present
~rlaterial possessing, a biological activity (for instance, con-
~:l taining i~mnobilized hygrolytin3~ in comparison with the conven-
; tional medicines traditionally used for treating pyo,-necrotic
wounds in soft tissue~ is illustrated by the following data
-` reported in Table 1 below-
T A B L E
Characteristic of D u r a t i o n of t r e a t m e n t (d a y s)
the treatment with the biologically with a native with a hyper-
process active material acc~d- enzyme tonic salt so
~! ing to the invention tion containi
'',' antiseptics
'~ Complete purification
'; of wounds an~ emergence
,~ of granulation islands 4.5 + 0.2 7.~ + o.5 9.5 + o.6
... ... Table 1 to be continued ... ...
` : ~:.
~, ~
,
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-18-
201122~
,
... ... Table 1 continued ... ...
Complete healing of the wound
from the be~innin~ of the
treatment 15.0 + 2.1 20.0 + 1.5 26.0 ~ 2.2
___ ______
The result~ of a clinic~l treatment have shown that the appli
cation of textile materials containing immobilized enzymes
for treating the patients affected with purulent surgical dis-
eases of tissues makes it possible to shorten the total period
of treatment by a factor of 1.3 to 1.8.
Enzymotherapy considerably reduces the period of beginning
of purification of wounds and emergence of granulations: by
a factor of 1.7 to 2.1.
The method for preparing the above-described material reside
in the following:
A textile material whi~h is in itself chemicall~ inert,is
subjected to the activation treatment to form therein reactive
functional groups until their content reaches o.o625 to 3.125
mg-equiv. per gram~ of the carrier. The~ activation process
depends on the chemical struature of a textile material (natu-
ral, artificial, Rynthetie fibre~) and o~ its textile structur~
(weaving method used, thiclcness and number of thread folds,
denstty of the textile material, etc.).
A cellulose- containin~ textile material is activated by
subjecting it to oxidation with an alkali metal periodate~
such as, for instance, sodium periodate, to form cellulose
dialdehyde. The activated textile material containg from o.o6z
to 3.1Z5 mg-equiv. of reactive functional groups per gram of
the carrier.
. ..
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20~ ~22a
~; Activation o* a te~tile Inaterial ;nade ~rom synthetic fibres
(i.e. a material containing no cellulose), such as, for instanc-
from polycaproami- fibre~" is carried out by subjecting a
carrier-~aterial to hydrolysis with an acid, followed by ~ashin~
the carrier thus-hydrolyzed with water and by treating it with
~' Q solution of a co~pound containing reactive functional groups
until the amount of the latter in the carrier reaches some
,
0.0625 to 0.3125 mg-equiv. per gram of the carrier. It is
advisable that strong mineral acids be used thereby, su~h as,
. . ~
for instance, hydrochloric or sulphuric acids. It is advisable
that the tre~tment o~ the hydrolyzed carrier made ~rom syntheti~
. .
fibres be carried out either by a solution of glutaric- aldehyde
followed by washing with water, ar by a solution o~ dimethyl
i sulphate-, followed by washing the carrier with ethyl alcohoI
;- and with a phosphate buffer solution.
~ Thereupon, the enzyme which is a biologically active prin-
:?. ciple is immobilized on the activated textile material from
buffer solutions having a pH ~f from 6.5 to 7.5 at room tem-
!`:j
, perature for 8 to 16 hours. Due to interaction between the
reactive groups joined to the textile material and the free
functional groups contained in the enzyme~, there is formed -~
~ between them a covalent chemiGal bond. As a result~ a textile
`i material is produced, carrying a chemically (covalently) -~
~-` immobilized thereon biologically active substance having a ~;
-~ prolonged action. The immobilization process is continued
~` until a biologically active textile material containing some ;
~, 0.02 to 0.5~0 of the enzyme based on the weight of the material,
is prepared.
:,
'','`~ :.
-20-
2~1~22~
The material obtaill~a in the form of cloth is squeezed out~
fiashed to remove the pilysically adsorbed enzyme, dried, and
placed into a tight containe.r, for instance, sealed into poly-
ethylene bags or paper-lined plastic packageR. Finally, the
material i5 sterilized by the per se known methods, such aR,
for instance, by irradiation or in a gaseous medium.
.,
~ Prior to sealing into containers, the material, if need be~j
may be shape~ to assume a form.convenient for use, such a~,
into napkins, lint, powder, etc., using the per se known methocl
The. above-described biologically active material prepared
by the above-disGlosed method may be used in a dressing means,
The-latter has the form of a bandage compri~ing~ successively
. arranged therein, a protective layer, an absorbing layer,
!,~, and a wound-adjoining layer, at least one layer in this bandage
;~
. being formed from the above-deRcribed material. The. advantage
~, offered by the present dressing means over the art-known dress-
ing.meanCf in the form of napkins made from similar biologically
active materials resides. in the fact that the form:er ensures
a fuller use of the therapeuti¢ efffefct of the immobilized
enzyme. This fact ~ explained by the presence of an absorbing
~'~,3 layer which constantly suc:ks off splitting products, wound
discharge and exudat:e, and which renders possible a longer
and more effective use: of the biologically acti~e material
constituting the wound-adjoining layer. For this reason, the
. patient feel~ no discomfort caused by the need for frequent
replacement of napkins wholly made from the biologically activf
material~ such napkins being quickly saturated with splitting
~,, ' .
~','' ' .
., -- .
-21-
201~22~
products, ~ound discharge and exudate.
In another embodiment of the ~resent dressing means, the
wound-adjoinin~ layer is made from the above-described biologi-
cally active material~ wllile the absorbing layer is made from
a textile ~oven, or non-woven, or l~nitted fabrie which does not
contain any biologically aetive substanee.
! In a yet another embodiment of the present dressing means,
the wound-adjoining layer is conYtituted by a biologically
~~ active material containing a proteolytie:~ or collagenolyti¢,
:~ or bacteriolytie enzyme, while.the absorbing layer i.s also
constituted by the same biologi¢ally active material containing
a collagenolytic, or a bacteriolytic enzymes.
For instance~ if the wound-adjoining layer is made from
~ the material containing a proteolyti~ enzyme, then,. the absorb- :~
I ing layer makes use of a material containing a collagenolytie~
or a baeteriolytie enzyme. If the wound-adjoining layer employs
a eollagenolytie enzyme, then, the absorbing layer employs
I a ba¢teriolytie enzyme, and if the wound-adjoining layer uses ~:
;1 a bacteriolytie enzyme~ the absorbing layer uses a collageno-
:l lytie enzym~
~' The present- dressing means ensures., simultaneously, splittin
I of neerotic masses~ liquefaetion of viscous dense exudate~ and
suppression of microbial growt.h in the wound.
An indi~idual. dressing means comprises elements intended
to fix it on the patient's body, such as, for instance, an
adhesi~e tape, a Velcro tape, etc.
. An indi~idual dressing means is prepared using conventional -
. : .
., .
~:
~ -~2-
:`` 20~ ~ 22~
technologies tradition~lly used in te-ctile and clotlling industr
For better understanding of the essence of the present inven
'~'
~ tion, attached herewith are specific ~xamples illustrative of
- the present metllod for preparing a blologically active material
.,j .
a dressing means, as well as of their application in practice.
EXA~PLE 1. Some 3.3 L of water were poured into a reactor,
:
j its stirrer was set into rotation, and 9.4 g of iodic acid
', were added.
Into another reactor, the same amount of waber was poured,
3
a stirrer was set to rotate, and 1.6 g of sodium hydroxide
were added. Both solutions were kept under stirring conditions
~` until complete dissolution of the crystals of the acid and
sodium~ hydroxide during 5 to 15 minutes.
, Thereupon, both solutions were poured into a single reactor,
.¦ stirred for 3 to 6 minutes to obtain a sodium periodate solutio
having a pH of 5Ø
; 1 kg of medical cotton gauze was placed into the solution
thus-prepared and held (activated) at room temperature for
;, 12 to 16 hours in the dark. Upon activation, the gauze was
` squeezed out, washed with 4 times x 10 L of water~ and squeezed
out again.
As a result of the activation treatment, there are formed
in the cotton gauze reacti~e functional groups, in the present
case, aldehyde groups, in an amount of 0.0625 mg-equiv. per
gram of the textile carrier.
~..
In order to prepare a phospllate buffer solution, two reactor
were also used. One of them was filled with 3.3 L of water and,
.`.j
.
.
-23-
2~ 1 22~
,
under stirring conditions, 5 g of potassium dihydrophosphate
were added thereto, while 37 g of sodium hydrophospllate were
added under stirring con~itions to the equal amount of water
in the other reactor. Stirring was continued until the crystal~
. ~ ,,
were totally dissolved for 10 to 20 minutes.
;~ Next, both solutions were poured to~ether into a single
reactor to produce a phosphate buffer solution with a plI of 7.5
0.4 g of an enzyme, in the present cas~ hygrolytin, were
added to the phosphate buffer solution thus-prepared under
stirring ~onditions until the enzyme was cornpletely dissolved
for 10 to 20 minutes. One kg of the activated cloth (i.e. ~;
dialdehyde cellulose) were placed into the reRulting solution
and held at room temperature for 12 hours, during which period
the enzyme imaobilization process takes place due to the emer-
gence of covalent chemical bonds. The cloth was then washed
until no protein traces were detected in the washings, whereupo ~-
the cloth wa~ squeezed out and dried in ai~ for 24 hours. As
a result, a biologically active material, in the present ca~e,
cotton cloth featuring a prolonged therapeuti¢ action, is pro-
ducad. The amount of the immobilized enzyme, in the present
case~ hygrolytin, as determined by the enzyme loss f~om the
solution, is 0.2 mg per gram of the textile cotton cloth, i.e.
accounts for 0.02dp of the weight of the cloth.
The dried material was shaped into medicinal forms, for
instance, into napkins having the desired size, sealed into
double polyethylene bags, and sterilized by ~-radiation usinF
the per se known procedures.
,
.
_2L~_
2 0112 h 3
L`~`IPL~ 2. A solution of sodi~Im perioclate was prepared
following the procedure described in E~;ample 1, and 80 g of
medical cotton gauze were placed into it. The process was
further c~rried out lollowing the procedure of Example l to ob-
,, .
` tain a cloth containing aldehyde groups in an amount of 0.78
mg-equiv. per gram of the textile cloth.
A phosphate buffer solutioI~ was prepared following the pro-
cedure described in Example 1, and 0.24 g of nn enzyme, in
~ the present case, hygrolytin, were added thereto. The process
'i
~ was further carried out following the procedure of Example 1.
:,
The amount of an immobilized enzyme~ i.e. hygrolytin, is
equal to 1.25 mg of the enzyme per gram of the textile carrier
(i.e. 0.125~o).
EXAMPLE 3. A solution of sodium periodate was prepared
following the procedure described in E~ample 1, and 20 g of
medical cotton gauze were plunged into it. The process was
further carried out ~ollowing the procedure of Example 1 to
obtain a cloth containing aldehyde groups i~ an amount of 3.125
mg-equi~. per ~ram of the cloth.
A phosphate buffer solution was prepared following thei proce
dure of Example 1~ and 0.192 g of nn enzyme, in the present
case, hygrolytin, were added thereto. The process was further
carried out following the procedure of Example 1.
The amount of the immobilized enzyme, i.e. hygrolytin, was
equal to 5 mg per gram of the cloth (i.e. 0~5~o)~
EXAMPLE 4. The process was carried out following the pro-
cedure described in Example 1, with the ex~!eption that terrilyt
i
'~'
-25-
201~ 220
was used as an enzyme. The ammunt of the im.mobilized enzyme~
in the present case, terrilytin, accounted for 0,02/o based on
the weight of the c.otton gauze.
EXAMPLE 5. The proces~ wa~ carried out following the pro-
~, cedure described in Example 1, with the exception that used
i as an enzyme was collagenase. The amount of the immobilized
- enzyme, in the pregent case, colla~enase~ accounted for 0.02~o
based on the weight of the cotton gauze.
EXAMPLE 6. The process was carried out following the pro-
c.edure described in Example 2 ~ with the exception that terrilyti.
,
was used as an enzyme~ The amount of the immobilized terrilytin ~...
accounted for 0~1 20a~ of the weight of the cotton gauze.
.,
: EXAMPLE 7. The proce~s was carried out following the proce-
~ dure described in Example 2, with the exception that collagenas~
. was used as an enzym.e. The amount of the immobilized collage- ~:
nase accounted for 0.140$ of the weight of the textile; gauze. :
E~AMPL~ 8. The process was carried out following the pro- .
cedure described in Example 3, with the exception that terri- :
lytin was used as a~l enzyme. The amount of the.immobilized
terrilytin accounted for 0.5~,~ based on the weight of the cotton
gauze.
EXAMPLE ~. The proce~s was carried out following the proce-
. dure described in Example 3~ with the exception that collagenas .
`- was used as an enzyme. The amount of the immobilized collagenas
. .
accounted for 0.5~ based on the weight of the gauze.
A~IPLE 10. The process was ~arried out following the ~. -
procedure described in Example 1., with t.he exception of the fa~ ~ .
' .
, -, .
'~
~.
-26-
2~ ~22~
,
that, as said texti].e material, use was made of a gauze from
cotton-and-viscose fibres.
E~Ai~IPLE 11. Th~ proces3 was carried out following the
~! procedure described in ~xample 2, with the exception tha~, as
i -
~ said textile material, use was made of a gauze made from cotton
; -and-viscose fibres.
EXAMPLE 12. The process was carried out following the pro-
cedure described in Example 3, with the exception that~ as said
textile carrier, use was made. of a gauze ma~e from cotton-and-
-vlscose fibres. ~-
EXAMPLE 1~. The process was carried out following the
procedure described in Example 1, with the exception that for
i preparing a buffer solution, 20.7 g of potassium dihydrophospha
and 11.~ g of sodium hydrophosphate were added to obtain a
phosphate buffer solution with a pll of 6.5.
EXAMPLE 14. The process was: carried out following the pro-
.~1 cedure described in Example 1, with the exception that for
~ preparing a buffer solution, 11.9 g of potassium dihydrophos-
:~ phate and 23.. 6 g of sodium hydrophosphate were added to obtain
-l a buffer pho3phate solution with a pH of 7.
E~AMPLE 15. The pro~ess was carried out following the pro-
~ cedure described in Example 1, with the exception that trypsin
. was used as an enzyme.
EXAMPLE 16. The process was carried out following the pro-
~ c.edure de3cribed in ~xample 1, with the exception that use :~
`! was made of a phosphate-citrate buffer solution having a pH ~.
1 of 7.5. Said solution was prepared using the following procedu ~
,,, . :-: .
'`1 ' '~" ~;~:
~ -27_
201122
:
Some 1.8 L of water were r~oured into the fir~t reactor, wher
'~ after 19.06 g of citric acid monohydrate l~ere added thereto
under ~tirrn~ conditioni3, whereas ~ome 8.25 L o~ water were
poured into the gecond reactor, followed by addition of 329.3 g
sodium hydrophosphate under stirring condi'ti.on~. Stirring
was continued until the complete~-aissolution was accompliished,
whereupon both 901ution8 were poured together.
The process wai~ further carried.out ~ollcwing the procedure
'. of Example 1.
EXAMPLE 17.'T~q-proc.e~g was carried out following the proce
dure deicribed i'n Example 13,. with the exception of the fact
~'~' that use was made of a phosphate-citrate bu~fer siolution. In
.- order to pr~pare: ~aid solution, 71'.7 ~ o~ ci'tric acia mono-hyd- :
-:` ratQ were. add'~d to 1.8 L of water poured into olle reactor under
' stirrin~, while 224.. 5 g of sodium hydrophosphate were added'
., to. 8.Z5 L o~ the water poured' into the other react:~r, also
.~ under ~t.irring. Upon complete s.olubilization of the sal~.s, the
',''':' solut:ions thus.-obtained: were pu~ together to obtain a buffer
~ solution ha~ing a pH = 6.5. The process was further carried
.,;~
, out following the procedure of' ED~mple: 13 .
., XAMPLE 18. ~h~-pro¢ess wa9 carried out following the pro-
', cedure de~cribed in Example 1~4 ~ with the exception of the fact
that, in order to prepare 'a phosphate-Gitrate buffer solution,
' 38.1 g o~ citric acid ~onohydrate. were added under stirring
.~................ condî'tionis to-1.8 L o~ wAter poured into one-reactor, while-
~:'! 290.5 ~ of sodiu~i hydrophoi~phate: were added to 8.25 L of water ~
,~! contained in the other reactor. A~ter the solubilization o~ ~ :
~:,
,~, :
,: ~ ~' : .': , . ' ' : : : ~ :
-28-
20~2~
tlle salts,both ~olution~ were put to~ot!~er to yield ~ buffer
solution llaving a pH = 7. The proceg~ wa~ ~urther carried out
following the procedure ~f Example 14.
EyA~prJE 19. Some 50 L of 3N-~Iydrochloric aGid were poured
into a reactor, and 1 kg of a knitted fabric ~ade from poly-
caproa~ide fibre~ were placed into it. Thereafter~ the acid
temperature was c~u~ed to rise up to 60 C, and the ~abric was
held at thi~.temperature~-~or 4 hours. Upon termination o~ the
hydrolysls, excess. hydrochloric acid l~a~ cooled down an~ dis-
earde~. The,knitted fabric was washed with water until no hydro-
chloric ac-id traces were dete.cted- in the washi~gs, Then, some
40 L o~ a 5~-~,lutaric aldehyde were poured into the reactor,
and 1 kg of the ~nitted fabri~ sub~ected to hydrolysis were
placed into it... The temperature o~ the:glutarie aldehyde 901u-
tlon.was brou~ht to 50 C and maintained at this: le~el ~or 4
hours. Then, the glutar~ aldehyde solution was c.ooled down
and discarded~ The fabric was wa~hed with water until no smell
.~.
~ of glutaric aldehyd~ was le~t. The,fabri~ acti~ation proces~
.
-~' wa~ thus terminated.
As a result of the activatio~ txeatment, there are formed ,.
, in the knitted fabri.~ reactive func.tional groups, in the pregent
', case, aldehyde groups, aontaining 0.. 0625 mg-equi~ per gram~
'. o~'the textlle fabriG..... ' '
Preparati.on of the phoiphate.-buffer solution was carried :-
,:
! out ~ollowin~ the proeedure o~'Example l. For this purpose, som~
: o.66 g Or an enzyme~ in the present case, terrilytin, were
.~ added.to the phosphate buPfer ~olution thuY-obtained at a pI~=7.
~., . :
. . .
:
~. -29-
20~ ~22~
~. . .
Stirrin~ was continued until complete qolubilization within
10 to 20 minutes.
1 kg of the activated lcnitted fabric made from polycaproamid
fibre~ were placed illtO the thus-prepared terrilytin solution
in the phosphats buff0r solution having a volume of 6.6 L and
an enzy~e concentration of 0.01%, and held at room temperature
for 9 ~ours. There took place the enzyme immobilization process
due to the formation of covalent chemical bonds. Thereupon,
the fabric-wa~. washed with a physiologic salt soIution and
water u~til no enzy~e (protein) traces. were detactable in
the washing~s, the a~ount of the enzyme (protein) being controll~
by the per se known procedures.
The fabric thus-treated was then ~.queezed out and dried in
! ~
3 air for 24 hours to obtai-n a biolo~ically active material, in
¦ the pre~ent case, a knitted polycaproamiae fabri~, featuring a
., .
~ prolonged`therapeutic ac.tion
1
~ The material thus-obtained oontains 0.02~ of im~obilized
;l ~errilytin ~i.e.. 0.2 mg of the enzyme per gram of the carrier).
Af*er drying~ the material was shape~ into medicinal forms,
¦ such as~ for instancel into napkin~ ha~ing a de~ired size,
ealed into a container, and: finally sterilized in a ga~eous
.I mediu~ using the per SQ known procedure~
EXAMP~E 20. An activated knittea polycaproamide fabric .
.3 was prepared followlng the procedure described ln E~a~ple 19, .
-~ wlth the exception that use was ~ade of a 10~p-glutaric. aldehyde
:
~:5 After acti~ation, the content of aldehyde groups in the fabric
.`! was 0.155 mg-equiY. per gram.of the fabric.
;., . ~
-3~~
20~1 2~
1 k~ of the activated fabric were placed into a reactor
c.ontaining 6.6 L of an 0.03/~-terrilytin solution in a phosphate
buffer solution having a pH = 7.5, and held at room temperature
. for 8 hours, Further~ the fabric was subJected to treatment
described in Example 1g. The biolo~ically acti~e material
~' thus-obtained contal~s o.6 mg of tsrrilytin per ~ra~ o~ the
fabric, i.e. o.o6dO based on the wei~ht o~ the fabric. The pro-
cess was continued following the procedure of Example 19.
. EXA~PL~ 21~. An acti~ated knitted po-lycaproamide ~abric
~ wa~ prepared following the proc.edure described` t'n Example 1-g,
: with the e~ception o~ the fact that ~ 15~-ælutari'c aldehyde
was usod. ~ter acti~ation, the content o~ aldehyde group3
~` in the fabric was 0.26 mg-equi~. per gram o~ the fabric.
1 kg of the acti~ated: fabric were placed into 6.6 g of an
;' 0.1~0-terrilytin solution in a phosphate bu~fer ~olution having ;.
,' a pH of'7.5, and held at roo~ temperature for 10 hours. Furthe~:! . . .
processin~ of the fabric was carried out following thff pro~e.
' dure.of Example 19.
The. resulting materi`al containg.2 mg of t'errilyt'in per gram ~'
~! of the carrier, i.e. 0.2~ of the enzyme basëd.on the weight
~`' o~ the fabric-
~'"' EXAMPLE 22-. The process was carried out. followi'ng the. :
~ procedùre described in Example 19, with the exception o~ the f; ~:
'. that, as an enzyme~ use was ~nade of trypsin. The material ::~
thus-preparea cont'ains 0.02~o 0~ immobilized trypsin on.the te~ :
~ tile carrier, in the present case., on the knitted fabri'c from
'.. ~ polycaproamide fibres.
., ' . ~:
~,'- ':,
: -31-
2~ ~22~
. - .
~ XA~PLE 2~. The process was carried out -fol:Lowlng the proce-
dure described in ~xample, with the sole e~ception that~ as an
enzyme, uge wa~ made of trypsin, and 1 kg of the activated
knitted polyc~proamdde ~abric were placed into 6.6 L of an
0.03~-tryp~in solution in a phosphate buffer solution and held
at room temperature for 9 hours. The~process was further conti-
nued~ folIowing the procedure af Example 20.
. The material thus-prepared: contained o.o6~ of trypsin based
:1 on the weight of the knitted polycaproamide fabric.
.~
.. 1 . E~AMPLE 24. The.pro~ess was ¢arried out following the pro-
cedure described in Example 212 w~t.h the sole exception of the
fact that the immobilization treatment was carried out in an
.l 0.15~-trypsin solution in a phosphate bu~fer solutio~
The: material thus-prepared contains 0.3~ of trypsi~ based
.l on the weight of the fabric.
~1
EXAMPLE 25. A polycaprQamide knitted fabric was held in ~..
a reactor filled with dimethyl sulphate at a bat.~ modulus of
~ 10 for 10 hours at roo~ temperature. The.excess dim.ethyl sul- .
`j phate.was poured out, whereafter the ~abri~ was~washe~ onee
with et.hyl alcohol at a bath modulus of 20 at a temperature :~ :
of 4 Ct followed by washing t.hrice with a phosphate buffer ~:
solution ha~ing a pH of 7.5 a~ a te~perature of ~ C. The fab-
ric thus-processed c.ontained reactive imidoethereàl ~rroups.
The immobilization treatment of the enzyme, in the present
L .
case, o~ trypsin, W~9 carrïed out. at a bath modulus cf 10
~rom an enzyme solution in ~ phosphate buffer solution having
a concentration af o.o4$ for 16 hours at room temperature.
,:~ "
.
2 0 ~ 1 2 2 ~
~ h~ resulting ~aterial contains 0.2~;~ of the im~Lobilize~
trypsin, i.e. 2 m~ per gra~ o~ the carrier.
The fabric was then washed wit'h a physiologic salt solution
and water until the washings contained no enzyme traces whose
amou~lt was controIled by the per se known procedures.
Thereupon~ the fabric was squeezed out and: dried in air
for 24 hours t-o yield a ~aterial, in the present case, a Xnitt~
,' polycaproamide.fabri~.~ featuring a biolo~ical acti~ity and a
prolon~ed therapeutic.action.
,' The~ ~aterial thus-prepared, after being drie.d, was shaped ,~ .
`,," into ~edicinal for~ns, su~h as, for instance,. into.napkins havin~ ,
-, a desired size, sealed into double-waIled poIyethylene bags,
'. and sterilized by gamma-rays using ~he per se k~own pro.c.edures.
~ EXA~IPLE 26~ The process was:carried out followin~ the proce~
dure dc~c~ibed in Example 2~, wlth t'he sole eYception of'the
fac~t that the immobilization treatment of trypsin, used a~ an :~
.", enzyme, was carri'ed'out in an 0.008%-trypsin solutïo~ i'n a
~ - phosphat'e buffer solution at a bath m.odulus of iO for. 12 hours~
::~ The:resuIting materi'al c:ontaine~ O.. Q4~ of the immobilize~ tryp-
;`~ sin, i.. e.. 0.4 mg per gram of the carrier
,, XAMPLE 27... The process was carrIed out following the, prQCe
dure described in Example Z5, wi'th the:sole excepti~n of the- :~
` ~aGt. that the immobilizatio-n treatment of trypsi~ was. performed
,. in an 0.024~-trypsin solution in a. phosphate:buffer solution
:.~ at- a bath modulus of 10 for 10 hours. The.material thus-obtaine
,. c:ontained 1.2 mg of trypsin per ~ram of the carrier, i.e. 0.12~,'~. ,.
of trypsin per gram of the carrier.
;"', :
` 33
2 0 ~ 1 rJ 2 3
~ XAMPL~ 28. The process was carried out following the proce
dure describe5d ia Example 19, with the exception that r a~ an
enzyme, use wa~ ~ade of l~sozyme. The resulting material contai
0 . 02~o by weight of immobiliz~d lysozyme.
FXA.~LE Z9. The process was carried out following the proce
dure de~c-ibed in E~asnpLe 20, with the exception that, as an
enzyme, u~e was made of lysozyme. The resulting material contai
ed o~o6~ by weight of immobilized lysozyme.
EXAMPLE 30. The pro~ess was carried out following the proce-
dure described in Example Z1, wïth the e~ception that, a~ an
enzyme, use wa~ made o~ lysozyme.The materiaI thus-prepared
contained 0.2~ by weight of immobilized lysozyme.
I EXAMPLE ~1. The proce~s was carried ou~ following the pro-
~'i :
cedure de~cribed in Example 19, with the exception that, as an
j enzyme, u~e was made o~ protosubtilin. The resulting material
a o.a2~ by weight of immobilized protosubtilin.
EXAMPLE ~2 . The proce~s wa~ ¢arried out followi~g the pro-
cedure described in Example 20, with the e~cept`ion that, as an
enzyme, use was made o~ protosubtilin. The mate~ial thus-prepa-
red containe~ o.o6~ by weigllt of immobilized pro$osubtilin.
EXAMPLE 3~. The proces~ wasi ~ar~ied out following the pro-
cedure de~cribed in Exa~pIe 21, with the exc~eption that~ as an
enzyme, use was made of protosubtilin to obtain a material
containing 0.2$ by weight of immobilized protosubtilin.
E AMPLE ~4 . The steriIe, biologically acti~e material, pre-
' pared following the procedure of Example 1, is a wo~en, medica]
-~, grade ? cotton gauze containing, immobilized thereon and co~alel
;,
, ~
`"'I ;~
:.
_3L~_
2~1122~
ly bound thereto, hygrolytin. The material contain~q 0.2 mg o~
hy~rolytin per ~ram of the woven cotton ~auze.
The material is turned out in the -form of medical napkins
and may be used for treatment of abscesses, phle~ons, postoper
tive compliGations af a surgical suture.
The uqie of this biologically active material ensure~ a pro-
longed thera~eutic effect of an enzyme for 48 to 96 hours,
wherea~ the life perio~ o~ a native enzyme which is used for
treatment of the ~ame aisQase~, iq not more than 1 hour. After
a therapeutic application of the claimed biologi¢ally acti~e
material, a complete healin~ of a pyo-necrotic wound on the -
soft tissue~ of a le~ is obser~ed after 17 days. In some ~ases,
during the first hours aft~r applying a bandage, the patient~
experienced a gentle feelin~ of burning, pricking of the wound
surface under the bandage. No allergi~ reactions of the patient
organiqms~ were obserYed~
It has been concluded that there exists a covalent type
of a bond between the carrier and the-enzyme; of the claimed
material~ proceeding ~rom the fact that after treating the
material with salt solutions, such as~ for instance~ with
sodium chloride, or with buffer solutions, such as, for instanc~
wit~h a pho~phate buffer ~olutionf the claimed material still
retained its enzymatic activity. In the course of such treat- -
~ment~ physiGally ad~orbed proteins ~enzymes) are washed out
of the carrier.
After five years of storin~ under normal conditions, the
claimed ~aterial still retained i~s therapeutic properties.
~ .
. ~ ,
~ 3 - ~
',tj ~
~35-
201122~
: EXAMPL~ ~5. The~ bio10r,~ically actl~e material prepared in
: ..
accordance with ~,xa~nple 1'had a composition identical to that
of Example 1, except that It contained 1..25 m~ o~ hygrolytin
per gram of woven cotton ~auze. T~e.therap~utic application
of thi4 wo~en cotton ~auze c.ontainin~ hygrolytin, immobllize~.
thereon and' ~ovalent.ly bound thereto., produced a prolonged
' therapeutic ac.tion which lasted some 48 to ~6 hours as compared :
,t! t:o an hour-long period of action of the natiYe enzyme,.
~ij .
.-', After apply~ng thi.s biologically acti~e material, a complete :~
healing, of a pyo-nec~toï¢.wound in the 50ft. tissues of a leg
wa~ obser~ed a~ter 15 days~ the other-results being a~lalogous ,
to those of Example 34. :
, EXAMPL~ 36. The bïologically acti~e material prepared in
'~ accordance with Example 1' had a GompOsitiOn ldentical to that ~.
~3 of Example 1:, exeept, that it containe~ 0.5 mg o~ hy~rolytin ~:
`'3 per gram of a woven ~i.otton gauze,. This material was applie~
`, in accordance with Example 24. After applieation of this biolo-
.,-. gically actiYe material, a complete healing o~ the wound
~, was obserYed after 14 days, the.other re~ults being analo~ous
~ to those of`Example 31l. ~
.~ EXAMpT,~ 3'7. The~biologically aotive materia? prepared ~:
in accordanGe with Example 1 had a compositi`on identicàl to
I that of ExampIe 1', except'that used as a textile carrier was
`1 a knitted.medical cotton gauze~ The results of the dedical ~.
''.¦ application of this material are the same as those of Example ~
..... .
~ EXAMPLE' ~8. The biolo~i¢ally acti~e material prepared in
7`'~' accorda~c-e with Example 1 had a composition identicaI to that
.~. 1 .
., .
:'1
-36-
2~1~ 22~
,
of ~ample 1, e~cept t~lat u~ed as a textile carrier was a non-
~ woven ~ate~R~ fabric ~rom. cotton fibres. The reslllts Or medica
.~ ~pplication ~ this material are the ~ame as those of ~xample 3
EXAMPLE ~., The biologically active material prepared in
accordance with Example 1 had a compositi'on identical to that
of Example 1', e~cept that used as a textile carrier was a wo~en .
, linen fabric-. The results of medical applicatIon of this mate-
,, rial are the sam,e as those of'Example 34~
E A~LE 40.. The biologically acti~e material prepared i`n
accordance with Example 1' had a cQmposition identical to that
. o~ Example 1:, except t.hat u~ed as a textile carrier was a
wo~en natural silk fabri~. The results of therapeutic.applica-
tlon of this material are the same as those o.f Example 34.
EXAMPL~ 41.~ The biologically a~ti~e material prepared i~
' ac.cordance with ~xample 1'9 had a composition identicai to that
'.~ of`Example 19', except tha~ used as a textile carrie~ was a :~
.. '' knitted' polycaproamide fabric.
~;! "" The results of the medical application of this material are '.
,, the same a~ those o~ Example 34.
~ EXAMPLE 42.~ The biologic.ally active material prepare.d in
`~. accordanG,e with Example 19 had a compo~ition identlcal to.that
of Example 1~, except that used' as a textile carrier~waR, a
''~ knitte~ polyurethane fabric~
~' The results o~ the medical application of this material wer~
. ` .
"~ the ~ame as those of Example 34.,
Example 4~. The,biologlcally acti~e material prepared in '~
accordance with Example 1 had a Gomposition identical to that
, .. . .
: -37-
2 ~ 2 ~
of ~xample 1, except that used as a textile carrier was a knitt(
viscose fabric.
The results of the medical application of this material were
the same as those of ~ample 34.
EXAMPLE 44.. The biologically active material prepared in
accordance witll Example 1 had a composition identical to that
Example 1, exeept that used as a textile carrier was a
secondary acetate cellulose knitted fabric.
The results of the medical application of this material were
the same as those. o~ Example 34.
E~AMPLE 45, The biologicalIy active material prepared in
accordance with Example 21 had a composition identical to that
of Example 21, except that it contained lysozyme. This material
contained 2 mg o~ lysozyme per gram of-the textile: carrier.
The use of this material containing immobilized lysozyme
covalently bound to the: earrier~ produced a prolon~ed therapeut-
~ action which lasted somc 48 to 96 hours against o~e hour-long
:i per~od o~ therapeutic a~tion of the native enzyme.
; After a medlcal application of this material, a c.omplete
healing of a pyo-necrotio wound in the.soft tissue~ was observe~
after 15 days.
Treatment of purulent. wounds at their hydration phase with
a textile materiaI containing immobilized lysozyme, shorten~
the period of elimination of the wound infection, cuts ~hort
- the alternative purulent inflammation, promotes the purificatio-
of wounds from pyo-ne¢rotic tissues~ stimulates the synthesis
. of glycogen and nucleic acids (DrJA and:RNA) in the woun~ cells,
i
.
~,~
~r
., -38- ,
~ 201122
.~ .
acti~ateg the proliferation of co~necti~e tissue cell~ (fibro-
. blasts), accelerates collagenosis, the contraction of wound
', . edges~ the contraction and epithelization of the wound.
., $XA~IPLE 46. The,biologically ac,ti~e material prepared in
"-, accordance with Example ~ ad a compositio~ identical to that
of Example 5.. This material c.ontained a collagenolytïc enzyme,
... namely, collagenase, in an ainoun~. of 0~2 ~g of colla~enase,
' per ~ram of the textile carrier~
~, After a medical appli¢ation of this materi'aL, a complete
: healing of the wound was observed after 16 days,~ the other
,~. results o~ the medical appli~ation of this material being ~.
analogous to those of Exa~ple~ 34 and.45.,
F~AMPLE 4:7,, The biologically active material,prepared in
~, accordance with Example 1"5 had a compositi`ou identical t~ that
' o~ Example 1
This ~at,erial was turned out in the form of lint having
;~ fibres 1.0 mm long and was,u~able for treatment of purulent,
deepS punctured wounds.
~- The therapeuti,c effect, nameIy, a complete heali'ng of wounds
,: . . .~ was ob~,erved a~ter 17 dàys.
.. EXAMPLE 48. The.biologically active material prepared in
accordan~.e wi`th Example 15 had a compositi,on identical to that
of Example 1'. ~:
This material was in the form of lint haYing fibres '.
~,i 8.0 mm long, and it was used to accelerate the treatment of
.~`I, dental infection foci, such ag, ~or instance, chronic granulate
periodonti~is.. This material in the form of lint produGes an
''`3 :
, `. . :
-39-
2~22~
antie~u~ative effect~ i~ acti~ely promotes the outflow oP exuda
through ~ tooth root channel ~even through curved, narrow, per-
meable channelsj.
E~MPLE 49. The biologically activ~ material prepared in
accordance with E~ample 15 had a composition identical to that
of ~xample 1.
The material thus-obtained was in the for~ o~ lint having
fibres 15 mm long, and it was used for treating an inflam~latory
process in the reGtum.
The therapeutic effect was observed. aft.er 16.5 days.
E AMPLE 50. Th~ blologically aGtive material prepared in
ac¢ordance with Exa~pie 15 had a~composition identical to that
!
of Example 1.
This material wa~ in the for~ of a powder Kaving a particle
size of 0.001 mm. It was used for treatin~ postoperative comp]i
~t cations of surgical ~u~ures.
After a medical applic.~t of this powde~ possessing a
~.i biological, includin~, an enzymatic activity, a complete healir
~ of the sut.ure was obser.ved after 17 days.
EXAMPLE ~. The- biologically active material prepared in
accordance with Example 15 had a composition identical to that.
.~ .
~ of ~xampl.e 1.
: This material was in the form of a powder having a particle
1 ~ize of 0.5 m~. It was used for treating pyo-necrotic processe
.. of complicated localizations and difficult-of-aGcess cavities.
, ~
The therapeutic effect was observed after 17 days.
.A.~PL~ 52. The-biologically active material prepared in
~,
,
.s:,:. . ..
- l~o~
201~22~
`: accordance with Example 15 had a com?osi tion identical to that
of ~xample 1 .
. This material was in the form pf a powder having a particle
size of 1.0 m~, and it wa~ used for treating phleg~ons.
. Tlie therapeutic effect was observed after 16.5 days,
EXAMPLE 53. A dressing means in the form of a bandage
consisting of three layers and a fixation member made in the
' form of an adhesive tape. The.bandage cQntained, arranged in
succession therein, a protective layer, an absorbing laye-r,
and a wound-adjoining layer..
~; The protective layer was made of a woven cotton gauze, while
the absorbing layer was made of three strata of a woven cotton
gau~e. The wound-adjoi~ing layer was also made o~ a woven
.! cotton ~auze: containing a co~alently bound:thereto, and immobi-
lized thereon~ proteo-lytic enzyme, namely, trypsin in an amount
of~ 0.02 wt.~
!~
ll of the above-mentioned.layers were laïd, in suc~ession,
one on top the other, tailored to form: napkins having a desirec ~.
size~ such as, for instance, 150 x 200 mm2 or 100 x 150 mm ~ :
interconnec:ted by some sewing method~ the fixation member
~I being atta¢hed to the protective layer. The dressing means
. thus-prepared was ~ealed into a c.ontainer and sterilized by
i~`;; exposin~ it to gamma-radiation,~ whereupon the dresi~g means
became ready for application and storing.
EXAMPLE 54~ The dressing means was ~ade in ac¢ordance
with Example 53 and contained an immobilized enzyme in an amou
of 0.125 wt.%.
. ~ .
,~ , ' ' :
- ::
,.i :: :
20~ 122~
E~A~I~L~ ~5. The (lr~ssing mcans was pr~pared in accordance
with E~ample 53 and contained an immobilized enzyme in an
amount of 0.5 wt,',l.
E'AMPLE 56. The dres3ing means was prepared in accordance
with ~xample 53 and contained an im:nobilized collagenolytic
enzyme, namely, collagenase, in an amount of 0~02 wt.~p.
XAMPLE 57. The. dressing means was prepa~ed in accordanee
with Example 53 and contained a Golla~enolyti~ enzyme an amount
of 0.140 wt.%.
,
EXAMPLE 58.The dressing means was prepared i~ accordance
with Example 53 and contained a ~ollagenolytie enzyme i~ an
` amount of 0.5 wt.~p~
. EXAMPLE 59. A dressing means in the form of a bandage c.o~-
- sisting o~ three layers and a fiYatio~ me~ber c.ontriv:ed as an
~`. adhesi~e tape. The band~ge~ containe~,. suc~essively arranged
therei~,. a prot:eet:i~e laye.~, an absorbing layer, and.a.woun*~
~ adjoining layer. The proteGti~e layo~ was made frQm a knitted
Q''`,~ '` textile fabric made from polycaproamide fibres. The: absorbing
layer waa.made ~rom four strata of a knitted vi.sc.ose fabric.
The wound-adjoining layer was. prepared from a knitted;poly-
eaproamide fabri~ containing. a co~alently immobilized bacterio-
lytie enzyme, ~iz. lysozyme, pre~ent. in an amou~t of 0.02~ by
weight.. Ths abov.e-specified layers were arranged in the claimed
dressing means in a manner identi~l to that of Example 5~. :
! EXAMPLE 60~ The dressing mean~ was prepared in accordanee
1~. '`
lS~ with ~xample 59 and had a lysozyme content of 0.12~ wt.,~.
..~j
X~PL~ 61. The dressing mean~ was prepared in.accordance
` 'i
f
,' -,
,: '
"
'
~',
. ^ ! ~: , . .
: .
-42-
2(~22~
with Example 59 and contained lysozyllle isl an alDount of 0.5
by weight.
XAMPLE 62. A dressing means in.the form of a bandage con-
sisting of three-layers and a Pixation member contri~ed as an
adhesive tape. The bandare contained, arranged in sucGession
therein, a protecti~e layer, an absorbin~ layer, and a wound-
adjoining layer~
The protective layer was formed from a non-woven glued hydro
phobic ~abric, while the absorbing layer was formed from three
strata of a non-woven glued hydrophilic fabric. The wound-
adjoining layer is formed from a single layer of`a knitted
textile fabric made from polycaproamide fibres and containing
: a covalentIy im~nobilized proteolytic enzyme, na~ely, trypsin,
in an amount of O.O~ wt .$.
The formati.on o~ the present dressing maans from the above-
enumerated layers followed~ the procedure of Example 53.
. F~-AMP~E 6~ The drcssing means was prepared in accordance
with ExampIe 62 and contained trypsin in an a~ount of 0.126
by weight.
;, EXAMPLE 64~ The dressing means was prepared in accordan~e
.~ with.Example 62 and contained trypsin in an amount of 0.5 wt.~.
~ XAMPLE 65. A dressing means in the form of a bandage
consisting of three layers and a fixation member formed as an
- adhesive tape. The bandage contained, successively arranged
therein, a protective layert an absorbing layer, and a wound~
adjoining layer.
~, The protecti~e layer was made from a wo~en cotton gauze, wh
, ~
. . . ~ .
-43-
20ll22a
the absorbing layer Wa3 made from cotton lint containing colla-
gonase on an a.~iount o~ 0.02',~ by weight and con~isting of flbres
:,
-~, . 1.0 mm long. Thc lint layer was dispo3ed on the interhal side
, of the,protecti~e layer of the bandage. The wound-adjoining
.~' layer was prepared from a wo~en cotton gauze c.ontaining co~alen
,~. . ,
ly immobilized hygroIytin an amount of 0.02~o by weight. The
,~ above-mentioned fabrics are laid one on top the other in such
~,,
,.-. a manner as to contain lint interlayers between the main layers
',~ whereafter the whole bandage i.s tailored into napkins. The
. . .
, , pro~edure of formi~g a dressin~ means containing such layers,
was identical to that of Example 53. :~
, , FXAMPL~ 66~ A dress,ing meansi was, prepared in accordanc,e
.
'~,; with Example 65, exc.ept that its~ absorbing laye~ was made
~ ' from a cotton lint containing lysozyme in an amount of 0.126~J
'~'' by wei~h~ and ha~ing fibres 10 min long~
..
EXAMPTE 67. A dressing means was. prepared. i~ accordance
with E~amplè 6$,~ except that its-absorbing layer was made from
a Gotton-~isco~e li~t contalning lysozymeinan amount of 0.5%
~,
,', by weight and haYing ~ibres 15 mm lon~
~ EXAMPLE 68.. A dressing mean~ was prepared in accordance.
,~ ' with E~ample 651 except.that its absorbing Layer was made from
.~ pulverulent, collagenase.in an amount: of 0.2% by weight and with
.~ a particle size of OrOOl mm~
;, ~YAMPL~ 69. A dressing means was prepare~ in accordance
with Example 65, except that its absorbing layer was made from
a pulverulent. collagenase.in an amount of 005~p by weigh~ and '~'~
'.' with a particle size of 0.1 mm.
. ' ' .
,, `
r ~ r
' . .A . ~ ' ' ' ' ' ~ ' '
_1~4 _
- 2~ 22~
r~XA`IPrE 70. A dressing means was prepared in accordance
with Examplo 65, except that its absorbin~ layer was made from
a pulverulent lysoz~me in an amount of o.5~10 by weight and
with~ a particle size of 1.0 mm.
EXAMPLE 71. A dressing means prepared in accordance with
Example 53 was applied at the sta6e of pre-medieal aid, just
after infliction of a trauma of soft tissues in the gluteal
regin, havin~ a size of 6 x 4 cm and 4 cm deep. Upon expira-
tion of 12 hours after infliction of the trauma, no oedema and
perifocal inflammation were observed; the internal surface
of the wound was clea~, and the ti~sue~ were ~iable. The comple
healing of the wound was observed after the sur~icaI treatment
in 14 days.
EXAMPLE 72. A dressing means prepared in accordance with E~
ple 54 was applied at the stage of pre-medical aid for treating
a trauma on the hi;p, havin~ a ~ize o~ 3 X 4 cm and about 3 cm
:,
deep. When 10 hours later the patient was admitted to the clini
,
no oedema and perifocal inflammation were obser~ed, and the
tissues were viable~ The complete healing of the wound a~ter
the surgical treatment was observed after 14 days.
XAMPLE ~3. A dressing means prepared in acoordan~e with
Example 55 wa~ applied at the stage of pre-medical aid fo~
treatlng a trauma o~ soft tissues, having a size of 5 x 2 cm
and a depth of up to 5 cm. When 11 hour~ later the patient
was admitted to the clinic, no oedema and perifocal inflammati
were observed; the internal surface of the wound waR: clean,
: ~:
and the tissueY were viable. The complete healing of the wound
-45-
20~ 2~
was observed aft~r the surgical treatment in 13 day3.
EXAMPL$ 74.. A dres~ing meanA was prepared in accordance
with ~xampl~ 53. Its wound-adjoilling layer was made from a
materiaI containing, immobilized thereon, trypsiin in an amount
of G ~2~o br weight, while its absorbi~g layer was made fro~.a
~ material Gontaining immobilized lysozyme in an a~ount of O.Z.
'~ by weight.. All of the layers o~ the bandage were in the for~
`' of napkins.
' Said dressing means wa~ applied. at the stage of pre-medical
!, aid for treating a trauma inflictsd to the soft Ieg tissues
ii~ and having a 9izc of 5 x 5 cm and a depth o$ 3 cm. When 9-
hour~ later after in~liction.of the trauma, the patient was
taken to the cliniG, the internal surface of the wound was
clean and no inflammatory effects were observed.
After the surgical treatment:" a complete healing of the
~ wound was observed in 12 daya.
s ~XAMPLE 75. A dreqsinæ meano prepared in accordance with
x Example 74 and having an absorbing layer constituted by a
stratum of lint'~ wa~ applied at the stage of pre-medicaI.ai~
for treating a trauma i'nflicted to the soft l'eg tissue~ and
having ~ size of 6 ~ 3 cm and a depth o.f 3 Gm. The patient
was admitted'to the clini~ 7 hours later, and a complete~
healing of the wound after its surgical treatment was obger~ed
in 12 days.
EXAMPLE 76. A dres3ing means prepared in accordancs wit.h
~xa~ple 74, except that its absorbing layer was made of lint,
was: applied under conditions identical to thoge of Example 7ll
' ,
.'
.`,''`
-l~6-
20~22~
A complete healing of the wound was obs:~rved after 11.5 day3.
,~AMPI,E 77. A dressin~ me.ans was prepared in accordance
with ';`xample 53. Its wound-~dJoining layer was made from a
material containing imMobllized colla~enase in an amount of
0.2',~ by weight, while its absorbin~ layer was made from a
~aterial containing immobilized lyso~y~e in an amount of 0.3
by wei~ht.
This dressing means was applied at the stage of pre-medical
aid for treatin~ a trauma inflic.ted to the soft leg ti~sues
and having a size of 3 x 3 cm and a depth of 2 cm. When 14 ~.
hours later the patient was admitted to the clini'c, the interna.
surface of the wound was.clean. A complete healing of the
wound after it,s sur~ical treatment. was observed in 12 days. ~ :
~XAMPLE 78. The process was conducte~ in accordance with
Example 1, except that for o~idation use was made of a potassiu
hydroxide solution and the activatio~ treatment was carried. ~:~
, ~
out for 16 hours. The material thus-prepared c.ontained an .
'.' immobilized enzyme in an amou~t of 0.02 wt.~. '.-~
~' EXAMPLE 7~. The process was conducted in accordance with :
., ~xample 3, except:that the duration of the~enzyme immobilixatio '
.~, treatmen*.was 16 hours~ The material thus-prepared~was subjecte
to additional mechanical treatment. in a mlll and turned out ~ ~
i~ the form of lint consisting o~ fibres 15 mm long. The enæyme ~ .
~ conte~t in this material was 0.5 wt.~p.
.. ~. F~AMPLE 80.. The proce~s wag c~rried: out in accordance with -~
'~ ~,xample 12, except that the duration of the enzyme immobili2ati
` treatment; was 16 hours and the final material was additionally ~ -
~ .
: .
.:~
, ., . ~ .
' , ; ~ . . . ~ . . . ': . ` , , . ' ' !
:.
-~7-
20~ 122a
subjected to mechanical treatment in a mill to yield a powder
having a particle size of ~..5 mm. The matorial contained 0.5$
by weight of an enzyme.
The material thu~-prepared was placed into a container by
the per se known methods~ sealed in it by the per ~e known
method~, sterilized by gamma-radiation and stored in packaged
condition at room temperature (i.e. at about.20 C)~ Under these
G.ondition~, the biologically active material retained its
therapeutic effiGacy during-5 years.
The data contai~ed i~ the above Examples are reported in
Tables 1-3 below.
~. ,
,
-4~-
2f~ ~f 22~
TAaLE 1. Characteristics of a biolo~ically active material
xamples Nos.
' 2 - .~nzyme content, per ccnt by weif~ht
;, 3 - textile materiaI
~1, 4 - raw materials
i,
j,f 5 - structure
`1 6 - natural
7 - synthetiG
~' 8 - man-made
..
'`i 9 - woven
10 - non-woven
11 - knitted :
12 - im~obilized enzyme
. 13 - proteolytic enzymes
' 14 - collagenolyti~ enzymes
j 15 - bacteriolytiG: enzymes ;
' 16 - length of fibres, mm
17 - lint
18 - powder
. ~, ' :.
.:, :
t ~
.,f
. . f
`f
_49_
2~ 22~
TABT,E 2. Parameters of the method for prcparing a biolo~i-
.~ cally acti~e ~aterial
.
1 - ~xample~ Mos..
$.;. 2 - textils material
3 - c:ellulose-containinig
4 - cellulose-non-Gontaining
?. 5 - natural
.~,,
6 - man-made
:
7 - syntheti~
` 8 - acti~ation
;, 9 - oxidation :
10 - hydroly~is
11 - reaction with a substance capabIe to form reacti~e ~un¢tio
nal groups; K and Na periodate
12 - aldehyde reacti~e fun~ctional ~roup~;
13 - conte~t:~ reacti~e functional groupsS wt~%
14 - acid-
., .
15 - washing with wate~
16 - reac.tion with a substance containing reactiYe ~unotional
groups
;-, 17 - glutaric aldehyde
` 18 - dimethyl sulphatQ
. 19 - waY~ing
.,
20 - washing with water
21 - washing with ethanol
22 - washing with a bu~fer solution
.......
. .,
-.:. .. - :
~?
.~
~50-
201i22~
T.~BI~ 2 continued ... ...
1 - E~ample~ Nos.
2 - activation
3 - hydrolysis
4 - content o~ reactive functional ~roups, wt.
5 - immobilizatio~
5 - enzyme
- proteolytic
8 - OEollagenolytic
9 - bacteriolytic,
10 - content, wt.~ -
11 - buffer ~olution ;
12 - room temperature
13 - duration, hours
14 - covalent bond between an enzy~e and a textile ¢arrier
15 _ 13 quO e z ing- O Ut
~: ;
-51-
2~122~
TA3LE 2 continued ... ...
Examples Nos.
2 - washing
3 - drying at room temperature
4 - shaping into medicinal forms
5 - bandage~
6 - napking:
7 - lint
8 - powder
g - sealing i~ a c.ontailler
10 - sterilization.
:
11 - with gamma-rays.
12 - in a gaseous ~edium
' 13 - storing~
.~ 14 - ïn paGkaged. condit:ïon
.,
:. 15 - at room temperature.
. ,
j 16 - up to 5 years.
!
.. .
.''~`` ,'.',
..
..-.
': ` '! '
~,, . '''.
~-3
.. . .
... ~ .
.
--s2 -
2 ~ 2 ~
TABL~ ~. Cllara~teri~tics of a dressing means
: ,:
xampl0s Nos..
2 - protecti~e layer
. 3 - textile material
4 - raw materials
5 - narural
- man-made-
7 - synthetic
. . :
- structure
9 - wove~
10 - non-wo~en
11 - knitte~.
12 - ab-sorbing layer~
13 - medicinal form
, .
14 - napkins
15 - raw materials
16 - natural
17 - man-made : :
18 - synthetic
19 - structure
20 - wo~e~
21 - non-wo~en
22 - lcnittod -~
23 - medic:inal form .~-
24 - napkins-
25 - lint:
26 - powder
::--~:
~.,. :: :: : :
,~. :
201~ 22~
T,~L~, 3 contirlued ,.. ...
1 - Examples- Nos~
2 - absorbing layer containing: an immobilized enzyme
3 - type of enzy~e~
4 - content, wt.~
5 - collagenolyti¢ enzy~nes
6 - ba~teriolytic enzyme~
7 - wound-ad~oining laye~
8 - textlle material
9 - raw materialcs
10 - natura~
11 - ma~-made
12 - synthetic
13 - structure
14 - woven
15 - non-wo~en ;~
16 - knitted
17 - medicinal form~ - napkins
18 - immobilized enzyme?
lg - proteolytic
20 - collagenolytic.
21 - bacteriolytic
22 - enzyme content, wt .~o
:
